摘要Background:Tumor recurrence severely impacts the prognosis of hepatocellular carcinoma(HCC)patients undergoing liver transplantation(LT).We aimed to explore novel and robust biomarkers for precise pre-diction of tumor recurrence and prognosis following LT.Methods:Cancerous tissues of 252 HCC patients who underwent LT across three centers were in-cluded in the study.Tissue microarrays and in situ hybridization were utilized to assess the circ0006646 level.Kaplan-Meier method along with the log-rank test was performed to analyze overall survival and recurrence-free survival.To identify prognostic factors,particularly related to tumor recurrence,we con-ducted univariate and multivariate Cox regression analyses.Nomogram was constructed to predict the risk of tumor recurrence after LT and subsequently the efficacy of the nomogram was validated.Results:Elevated circ0006646 levels in HCC were associated with reduced survival and increased recur-rence rates following LT(5-year overall survival:29.2%vs.60.4%,P<0.01;5-year recurrence-free sur-vival:42.3%vs.63.0%,P<0.001).High circ0006646 expression was significantly correlated with higher Child-Pugh grade(P=0.040),larger total tumor diameter(P=0.033),and beyond the Milan criteria(P=0.033).Cox regression analysis unveiled that circ0006646 expression score,preoperative transarterial chemoembolization(TACE),positive HBsAg status,poor tumor differentiation and beyond the Hangzhou criteria were independent risk factors for post-transplant tumor recurrence,leading to the development of a novel nomogram for precise prediction.The nomogram demonstrated a reasonable prognostic effec-tiveness(area under the receiver operating characteristic curve=0.7636,C-index=0.745)and outper-formed conventional models like the Milan criteria.Besides,the inclusion of circ0006646 enhanced the precision of the Milan and Hangzhou criteria.Moreover,circ0006646 served as a potent biomarker in alpha-fetoprotein(AFP)-negative HCC undergoing LT.Conclusions:circ0006646 is a novel and robust prognostic biomarker for predicting post-transplant sur-vival and tumor recurrence in HCC patients.A nomogram integrating circ0006646 stands as a valuable prognostic instrument in LT for HCC.